The role of bronchoalveolar hemostasis in the pathogenesis of acute lung injury.
Disturbed alveolar fibrin turnover is intrinsic to acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and pneumonia and is important to its pathogenesis. Recent studies also suggest disturbed alveolar fibrin turnover to be a feature of ventilator-induced lung injury (VILI). The mechanisms that contribute to alveolar coagulopathy are localized tissue factor-mediated thrombin generation, impaired activity of natural coagulation inhibitors, and depression of bronchoalveolar urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. Administration of anticoagulant agents (including activated protein C, antithrombin, tissue factor-factor VIIa pathway inhibitors, and heparin) and profibrinolytic agents (including plasminogen activators) attenuate pulmonary coagulopathy. Several preclinical studies show additional anti-inflammatory effects of these therapies in ALI/ARDS and pneumonia. In this article, we review the involvement of coagulation and fibrinolysis in the pathogenesis of ALI/ARDS pneumonia and VILI and the potential of anticoagulant and profibrinolytic strategies to reverse pulmonary coagulopathy and pulmonary inflammatory responses.
Hofstra
Jorrit-Jan H
JJ
Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. j.j.hofstra@amc.uva.nl
Haitsma
Jack J
JJ
Juffermans
Nicole P
NP
Levi
Marcel
M
Schultz
Marcus J
MJ
D055371:Acute Lung Injury / Q000097:blood* / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D010960:Plasminogen Activators / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000503:physiopathology*; D018179:Receptors, Thrombin / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism
D016207:Cytokines; D018179:Receptors, Thrombin; D005337:Fibrin; D010960:Plasminogen Activators; D013917:Thrombin